Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Christos Tziotzios; Christos Petridis; Nick Dand; Chrysanthi Ainali; Jake R. Saklatvala; Venu Pullabhatla; Alexandros Onoufriadis; Rashida Pramanik; David Baudry; Sang Hyuck Lee; Kristie Wood; Lu Liu; Seth Seegobin; Gregory A. Michelotti; Su M. Lwin; Evangelos A. A. Christou; Charles J. Curtis; Emanuele de Rinaldis; Alka Saxena; Susan Holmes; Matthew Harries; Ioulios Palamaras; Fiona Cunningham; Gregory Parkins; Manjit Kaur; Paul Farrant; Andrew McDonagh; Andrew Messenger; Jennifer Jones; Victoria Jolliffe; Iaisha Ali; Michael Ardern-Jones; Charles Mitchell; Nigel Burrows; Ravinder Atkar; Cedric Banfield; Anton Alexandroff; Caroline Champagne; Hywel L. Cooper; Sergio Vañó-Galván; Ana Maria Molina-Ruiz; Nerea Ormaechea Perez; Girish K. Patel; Abby Macbeth; Melanie Page; Alyson Bryden; Megan Mowbray; Shyamal Wahie; Keith Armstrong; Nicola Cooke; Mark Goodfield; Irene Man; David de Berker; Giles Dunnill; Anita Takwale; Archana Rao; Tee-Wei Siah; Rodney Sinclair; Martin S. Wade; Ncoza C. Dlova; Jane Setterfield; Fiona Lewis; Kapil Bhargava; Niall Kirkpatrick; Xavier Estivill; Catherine M. Stefanato; Carsten Flohr; Timothy Spector; Fiona M. Watt; Catherine H. Smith; Jonathan N. Barker; David A. Fenton; Michael A. Simpson; John A. McGrath

doi:10.1038/s41467-019-09117-w

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Christos Tziotzios, Christos Petridis, Nick Dand, Chrysanthi Ainali, Jake R. Saklatvala, Venu Pullabhatla, Alexandros Onoufriadis, Rashida Pramanik, David Baudry, Sang Hyuck Lee, Kristie Wood, Lu Liu, Seth Seegobin, Gregory A. Michelotti, Su M. Lwin, Evangelos A. A. Christou, Charles J. Curtis, Emanuele de Rinaldis, Alka Saxena, Susan HolmesMatthew Harries, Ioulios Palamaras, Fiona Cunningham, Gregory Parkins, Manjit Kaur, Paul Farrant, Andrew McDonagh, Andrew Messenger, Jennifer Jones, Victoria Jolliffe, Iaisha Ali, Michael Ardern-Jones, Charles Mitchell, Nigel Burrows, Ravinder Atkar, Cedric Banfield, Anton Alexandroff, Caroline Champagne, Hywel L. Cooper, Sergio Vañó-Galván, Ana Maria Molina-Ruiz, Nerea Ormaechea Perez, Girish K. Patel, Abby Macbeth, Melanie Page, Alyson Bryden, Megan Mowbray, Shyamal Wahie, Keith Armstrong, Nicola Cooke, Mark Goodfield, Irene Man, David de Berker, Giles Dunnill, Anita Takwale, Archana Rao, Tee-Wei Siah, Rodney Sinclair, Martin S. Wade, Ncoza C. Dlova, Jane Setterfield, Fiona Lewis, Kapil Bhargava, Niall Kirkpatrick, Xavier Estivill, Catherine M. Stefanato, Carsten Flohr, Timothy Spector, Fiona M. Watt, Catherine H. Smith, Jonathan N. Barker, David A. Fenton, Michael A. Simpson, John A. McGrath

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Abstract

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.

Original language	English
Article number	1150
Pages (from-to)	1-9
Number of pages	9
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-09117-w
Publication status	Published - 8 Mar 2019

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Final Published VersionFinal published version, 1.68 MBLicence: CC BY

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Tziotzios, C., Petridis, C., Dand, N., Ainali, C., Saklatvala, J. R., Pullabhatla, V., Onoufriadis, A., Pramanik, R., Baudry, D., Lee, S. H., Wood, K., Liu, L., Seegobin, S., Michelotti, G. A., Lwin, S. M., Christou, E. A. A., Curtis, C. J., de Rinaldis, E., Saxena, A., ... McGrath, J. A. (2019). Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02. Nature Communications, 10(1), 1-9. Article 1150. https://doi.org/10.1038/s41467-019-09117-w

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title = "Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02",

abstract = "Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.",

author = "Christos Tziotzios and Christos Petridis and Nick Dand and Chrysanthi Ainali and Saklatvala, {Jake R.} and Venu Pullabhatla and Alexandros Onoufriadis and Rashida Pramanik and David Baudry and Lee, {Sang Hyuck} and Kristie Wood and Lu Liu and Seth Seegobin and Michelotti, {Gregory A.} and Lwin, {Su M.} and Christou, {Evangelos A. A.} and Curtis, {Charles J.} and {de Rinaldis}, Emanuele and Alka Saxena and Susan Holmes and Matthew Harries and Ioulios Palamaras and Fiona Cunningham and Gregory Parkins and Manjit Kaur and Paul Farrant and Andrew McDonagh and Andrew Messenger and Jennifer Jones and Victoria Jolliffe and Iaisha Ali and Michael Ardern-Jones and Charles Mitchell and Nigel Burrows and Ravinder Atkar and Cedric Banfield and Anton Alexandroff and Caroline Champagne and Cooper, {Hywel L.} and Sergio Va{\~n}{\'o}-Galv{\'a}n and Molina-Ruiz, {Ana Maria} and Perez, {Nerea Ormaechea} and Patel, {Girish K.} and Abby Macbeth and Melanie Page and Alyson Bryden and Megan Mowbray and Shyamal Wahie and Keith Armstrong and Nicola Cooke and Mark Goodfield and Irene Man and {de Berker}, David and Giles Dunnill and Anita Takwale and Archana Rao and Tee-Wei Siah and Rodney Sinclair and Wade, {Martin S.} and Dlova, {Ncoza C.} and Jane Setterfield and Fiona Lewis and Kapil Bhargava and Niall Kirkpatrick and Xavier Estivill and Stefanato, {Catherine M.} and Carsten Flohr and Timothy Spector and Watt, {Fiona M.} and Smith, {Catherine H.} and Barker, {Jonathan N.} and Fenton, {David A.} and Simpson, {Michael A.} and McGrath, {John A.}",

note = "We acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration (NIHR-RD TRC) and by the NIHR Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. ",

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doi = "10.1038/s41467-019-09117-w",

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Tziotzios, C, Petridis, C, Dand, N, Ainali, C, Saklatvala, JR, Pullabhatla, V, Onoufriadis, A, Pramanik, R, Baudry, D, Lee, SH, Wood, K, Liu, L, Seegobin, S, Michelotti, GA, Lwin, SM, Christou, EAA, Curtis, CJ, de Rinaldis, E, Saxena, A, Holmes, S, Harries, M, Palamaras, I, Cunningham, F, Parkins, G, Kaur, M, Farrant, P, McDonagh, A, Messenger, A, Jones, J, Jolliffe, V, Ali, I, Ardern-Jones, M, Mitchell, C, Burrows, N, Atkar, R, Banfield, C, Alexandroff, A, Champagne, C, Cooper, HL, Vañó-Galván, S, Molina-Ruiz, AM, Perez, NO, Patel, GK, Macbeth, A, Page, M, Bryden, A, Mowbray, M, Wahie, S, Armstrong, K, Cooke, N, Goodfield, M, Man, I, de Berker, D, Dunnill, G, Takwale, A, Rao, A, Siah, T-W, Sinclair, R, Wade, MS, Dlova, NC, Setterfield, J, Lewis, F, Bhargava, K, Kirkpatrick, N, Estivill, X, Stefanato, CM, Flohr, C, Spector, T, Watt, FM, Smith, CH, Barker, JN, Fenton, DA, Simpson, MA & McGrath, JA 2019, 'Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02', Nature Communications, vol. 10, no. 1, 1150, pp. 1-9. https://doi.org/10.1038/s41467-019-09117-w

TY - JOUR

T1 - Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

AU - Tziotzios, Christos

AU - Petridis, Christos

AU - Dand, Nick

AU - Ainali, Chrysanthi

AU - Saklatvala, Jake R.

AU - Pullabhatla, Venu

AU - Onoufriadis, Alexandros

AU - Pramanik, Rashida

AU - Baudry, David

AU - Lee, Sang Hyuck

AU - Wood, Kristie

AU - Liu, Lu

AU - Seegobin, Seth

AU - Michelotti, Gregory A.

AU - Lwin, Su M.

AU - Christou, Evangelos A. A.

AU - Curtis, Charles J.

AU - de Rinaldis, Emanuele

AU - Saxena, Alka

AU - Holmes, Susan

AU - Harries, Matthew

AU - Palamaras, Ioulios

AU - Cunningham, Fiona

AU - Parkins, Gregory

AU - Kaur, Manjit

AU - Farrant, Paul

AU - McDonagh, Andrew

AU - Messenger, Andrew

AU - Jones, Jennifer

AU - Jolliffe, Victoria

AU - Ali, Iaisha

AU - Ardern-Jones, Michael

AU - Mitchell, Charles

AU - Burrows, Nigel

AU - Atkar, Ravinder

AU - Banfield, Cedric

AU - Alexandroff, Anton

AU - Champagne, Caroline

AU - Cooper, Hywel L.

AU - Vañó-Galván, Sergio

AU - Molina-Ruiz, Ana Maria

AU - Perez, Nerea Ormaechea

AU - Patel, Girish K.

AU - Macbeth, Abby

AU - Page, Melanie

AU - Bryden, Alyson

AU - Mowbray, Megan

AU - Wahie, Shyamal

AU - Armstrong, Keith

AU - Cooke, Nicola

AU - Goodfield, Mark

AU - Man, Irene

AU - de Berker, David

AU - Dunnill, Giles

AU - Takwale, Anita

AU - Rao, Archana

AU - Siah, Tee-Wei

AU - Sinclair, Rodney

AU - Wade, Martin S.

AU - Dlova, Ncoza C.

AU - Setterfield, Jane

AU - Lewis, Fiona

AU - Bhargava, Kapil

AU - Kirkpatrick, Niall

AU - Estivill, Xavier

AU - Stefanato, Catherine M.

AU - Flohr, Carsten

AU - Spector, Timothy

AU - Watt, Fiona M.

AU - Smith, Catherine H.

AU - Barker, Jonathan N.

AU - Fenton, David A.

AU - Simpson, Michael A.

AU - McGrath, John A.

N1 - We acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration (NIHR-RD TRC) and by the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.

PY - 2019/3/8

Y1 - 2019/3/8

N2 - Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.

AB - Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.

UR - http://www.scopus.com/inward/record.url?scp=85062608386&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09117-w

DO - 10.1038/s41467-019-09117-w

M3 - Article

C2 - 30850646

SN - 2041-1723

VL - 10

SP - 1

EP - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1150

ER -

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

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